Abstract
BackgroundOesophageal cancer is one of the most common and deadly cancers worldwide, being the sixth most common cause of cancer-related death. The curative treatment for gastroesophageal tumours focuses on surgery, although neo-adjuvant therapy is frequently recommended in all but the earliest tumours. Some aspects of staging early oesophageal cancer (EOC) and its surgical approach are under debate since the introduction of organ preserving techniques for management and treatment of these tumours.
Aim
This is a self-contained three-part project with an overriding theme towards improving the treatment and management of patients with operable gastro-oesophageal adenocarcinomas. The aim is approached by each study starting with the analysis of staging investigations, further assessment of treatment options and concludes with a proposed algorithm of enhanced clinical management. The studies assess accuracy of staging investigations and understand their utility in patients with EOC; compare outcomes between oesophagectomy, the historical treatment of choice, to endoscopic eradication therapy (EET); and finally introduce a novel approach for locally advanced oesophagogastric tumours.
Methods
A large single centre prospective database of patients treated for EOC with either surgery, EET or both between 2000-2019 was analysed to assess the accuracy of staging, and to compare outcomes after oesophagectomy and EET. Following this, consecutive patients treated with a novel technique, laparoscopic left thoracoabdominal oesophagectomy (LLTA),operated on during 2013-2019 were described, and outcomes were compared to the national standards (NOGCA).
Results
In the first cohort study, a total of 297 patients (Endoscopic mucosal resection [EMR] n=184; oesophagectomy n=113 [preceded by EMR n=23]) were included. Staging patterns for both groups were similar throughout all staging modalities (computed tomography (CT), endoscopic ultrasound (EUS), positron emission tomography (PET-CT)), showing low overall accuracy. In the EMR group, over-staging that might have changed management occurred in 10 patients (3.6%) for T-staging (T2) and 14 patients (5.0%) for positive lymph node-staging (N+). In the oesophagectomy alone group lymph node metastasis identified following surgery was rare (n=8 [8.9%]) and staging sensitivity for these surgically treated patients was low (CT 12.5%, EUS 12.5%, PET-CT 0.0%). Overall, PET-CT and EUS changed decision-making in less than 1% of patients with a clear CT and low risk histology criteria on EMR specimen.
For the second study, among 269 patients, 133 underwent oesophagectomy and 136 received EET. Adjusted survival analysis showed no difference between groups regarding all-cause mortality (HR 1.85, 95% CI 0.73, 4.72) and disease-specific mortality (HR 1.10, 95% CI 0.26, 4.65). In-hospital and 30-day mortality was 0% in both groups. The surgical group had a significantly higher rate of complications (Clavien–Dindo >3 26.3% vs. endoscopic therapy 0.74%), longer in-patient stay (median 14 vs. 0 days endoscopic therapy), and higher hospital costs (£16 360 vs. £8786 per patient).
Finally, the series analysing main outcomes after LLTA report 74 consecutive patients with a median inpatient stay of 10 days (NOGCA 9) for predominantly locally advanced gastro-oesophageal junction (GOJ) tumours (92%), the procedure had low postoperative morbidity, Clavien–Dindo (C–D) 0 in 52.7% patients, and a median number of total lymph nodes (LN) excised of 28 (NOGCA>15); LN % yield ≥ 18 was 90% (NOGCA 82.5%). Hospital and 30-day mortality was 1.4% (NOGCA 2.7%) and recurrence after LLTA was 25.7% at a median of 311 days.
Conclusion and expected outcomes
Staging accuracy is low in EOC and the addition of EUS and PET-CT does not change patient decision making significantly. Histology obtained from EMR specimens contains important predicting factors that do change patient management, proving to be an excellent staging tool rather than imaging techniques. Hence, EUS and PET-CT should only be used selectively in patients being assessed for EOC. Primary endoscopic therapy does not compromise oncological outcomes, with the added benefits of fewer complications, shorter hospital stay, and lower costs compared to surgery. It should therefore be available as a gold standard treatment for patients with early tumours although patients with adverse prognostic features may still benefit from oesophagectomy. The LLTA series demonstrates a novel, safe and reproducible left sided approach for cancer of the GOJ, with advantages such as better exposure of the hiatus, improved operating time and avoidance of the division of the costochondral junction and low thoracotomy, when compared to other surgical approaches.
| Date of Award | 1 Aug 2023 |
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| Original language | English |
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| Supervisor | Andrew Davies (Supervisor) & James Gossage (Supervisor) |